The magnitude of brain lipid peroxidation correlates with the extent of degeneration but not with density of neuritic plaques or neurofibrillary tangles or with APOE genotype in Alzheimer's disease patients

Numerous post mortem studies have demonstrated increased accumulation of li pid peroxidation products in diseased regions of Alzheimer's disease (AD) b rain; however, few have used techniques that quantify the magnitude of lipi d peroxidation in vivo. F-2-isoprostanes (F-2-IsoP's) are exclusive product s of free radical-mediated peroxidation of arachidonic acid, and their quan tification has been widely used as an ill vivo biomarker of the magnitude o f lipid peroxidation, We have determined F-2-IsoP concentrations in lateral ventricular fluid (VF) from 23 AD and 12 age-matched controls and correlat ed these with neuropathological and genetic markers of AD. VF F-2-IsoP leve ls were significantly elevated in AD patients compared with controls (p < 0 .01) and were significantly correlated with three different measures of bra in degeneration: reduction in brain weight (p < 0.01), degree of cortical a trophy (p < 0.01), and Braak stage (p = 0.02). When analysis was restricted to AD patients only, VF F-2-IsoP levels still were significantly correlate d to reduction in brain. weight and degree of cortical atrophy (p < 0.05). VF F-2-IsoP concentrations were not related to density of neuritic plaques or neurofibrillary tangles in seven brain regions, or to the number of epsi lon 4 alleles of the apolipoprotein E gene (APOE), These data suggest that the magnitude of brain lipid peroxidation is closely related to the extent of brain degeneration in AD but is not significantly influenced by the dens ity of neuritic plaques or neurofibrillary tangles, or the number of epsilo n 4 alleles of APOE.